Plasma Free Fatty Acids and Risk of Heart Failure

Abstract

Background Although plasma free fatty acid (FFA) concentrations have been associated with lipotoxicity, apoptosis, and risk of diabetes and coronary heart disease, it is unclear whether FFA levels are associated with heart failure (HF). Methods and Results To test the hypothesis that plasma concentration of FFA is positively associated with incident HF, we prospectively analyzed data on 4248 men and women free of HF at baseline and aged 65+ years from the Cardiovascular Health Study. FFA concentration was measured in duplicate by the Wako enzymatic method. Incident HF was validated by a centralized Events Committee. We used Cox proportional hazards to estimate the hazard ratio of HF per standard deviation (SD) of FFA. During a median follow up of 10.5 y, 1,286 new cases of HF occurred. In a multivariable model adjusting for clinic site, comorbidity, demographic, anthropometric, and lifestyle factors, each SD (0.2 mEq/L) higher plasma FFA was associated with 12% (95% CI: 6% to 19%) higher risk of HF. Controlling for time-varying diabetes and coronary heart disease did not change the results [HR per SD: 1.16 (95% CI: 1.09–1.23)]. Conclusions A single measure of plasma FFA obtained later in life is associated with a higher risk of HF in older adults. Additional studies are needed to explore biologic mechanisms by which FFA may influence the risk of HF and determine whether FFA could serve as a novel pharmacological target for HF prevention.

Cerebrospinal Fluid Free Fatty Acid Levels Are Associated with Stroke Subtypes and Severity in Chinese Patients with Acute Ischemic Stroke

“…The baseline level of FFA in CE stroke patients was approximately 2.5-fold higher than that of non-CE stroke patients, which was supported by Choi et al (5). Furthermore, we found that the FFA levels M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 10 increased as the severity of stroke increased, which was defined by the NIHSS score and infarct volume. Those positive trends still existed even after correcting for possible confounding factors.…”

“…An elevated FFA concentration is linked to several risk factors for atherosclerosis (5), including acute myocardial infarction (17), cardiovascular disease (8), heart failure (10), and atrial fibrillation (AF) (16). Pathological processes, including ischemia and subarachnoid hemorrhage, result in significant increases in brain concentrations of free fatty acids (FFAs) in animal studies (13).…”

Effect of intravenous l-carnitine in Chinese patients with chronic heart failure

“…27,28 This process may override the beneficial effects of correcting carnitine insufficiency since the increase in some acyl-carnitine derivatives in plasma may have a detrimental effect on cardiovascular function. 29,30 The paradoxical dose-effect relationship of carnitine on plasma triglycerides, showing a beneficial effect at low doses that disappears at high doses, 31 may be due to a similar mechanism; (ii) an increase in oral dose of carnitine above a critical level is associated with an increase in plasma trimethylamine 32 which may promote atherosclerosis. 33 Our results are not relevant to the first treatment approach based on carnitine insufficiency since the increased risk of developing major cardiac AEs has only been detected in humans with carnitine plasma concentrations .45.1 mmol/L.…”

Visceral Adiposity and Left Ventricular Mass and Function in Patients With Aortic Stenosis: The PROGRESSA Study

“…14 Moreover, a recent study in a large US population reported an association between plasma concentration of free fatty acid, which is typically elevated in patients with visceral obesity, and the incidence of heart failure. 15 The findings of this study thus suggest that development of LV hypertrophy in AS patients is not solely determined by the magnitude of LV pressure overload, but is also, in large part, related to the total amount as well as the regional distribution of body fat.…”